Bipolar affective disorder (BPAD; manic-depressive illness) is a common psychiatric disorder with primary features of recurrence (cyclicity) and swings (polarity) from high to low for both mood and energy. The highest risk among relatives is for BP I with a definite episodic nature. This mood disorder can shift from “mania to melancholia” or from high affectivity and excitement to the profound low energy and sadness of depression1-3. BPAD affects 1-2% of the global population and is associated with a high risk of suicide.
Twin, family, and adoption studies have all provided strong evidence for an important genetic component in the susceptibility to develop BPAD4, 5. However, like in other common medical illnesses, objective biological markers have not been identified for BPAD, and genetic studies have had to rely on clinical diagnoses. Genetic heterogeneity, phenocopies, genotyping errors, and the complexities of performing and interpreting statistical analyses may have contributed to some of the inconsistences observed in the genetic studies6. Despite compelling clinical-epidemiologic evidence from many investigations supporting a significant genetic susceptibility to develop BPAD, identification of the genetic variants or an underlying molecular mechanism causing BPAD has remained elusive7-13.